GENERAL PRINCIPLES OF INFECTIOUS DISEASES

Department of Infectious Diseases,

the Third Affiliated Hospital

Li Gang ( 李刚）2009.2

Introduction · Definition of infectious diseases and communicable diseases. · Distinction between infectious diseases and communicable diseases.

Definition:

1. Infectious disease: any infection caused by microbes or parasites.

2. Communicable disease: infection transmitted from persons or animals to other persons.

The goal of studying infectious disease:

1. To study etiology, epidemiology, pathogenesis, clinical manifestations, treatment and prevention of infectious diseases. 2. To control and eliminate these diseases. (occurrence, spreading, prevention)

Infection and immunity

The concept of infection The course of struggle between pathogens and human or animal bodies (host).

Pathogens:(microbes, parasites)

Prion; virus; chlamydia; rickettsia; bacteria; fungus; spirochete.

Protozoa; helminth.

1977 Hantaan virus1977 Ebola virus1982 E coli O157 ： H71983 HIV1986 CJD1988 HEV1989 HCV1992 Vibrio cholerae O139 strain1997 H5N12003 SARS coronavirus

Emerging pathogens and infectious diseases

Three kinds of infection

⑴ Commensal infection: Pathogens live in the host but don’t induce pathologic changes.

⑵ Opportunistic infection: Pathogens within the host can induce pathologic changes if host immunity is suppressed by some factors.

⑶ Pathogenic infection: According to the severity of the pathologic changes, several degrees in clinical manifestation from mild, moderate to severe will occur.

Infection status:

Primary infection

re-infection

co-infection

super infection

secondary infection

Manifestations of Infection Process

Entrance and colonization of pathogens will lead to the

following results.

1. Elimination: pathogens were excluded out by host nonspecific or specific immunity. Such as Candida albicans Escherichia coli

2. Covert (subclinical) infection:

￭ Most frequently occurs in

healthy individuals.

￭ The outcomes will be:

A. Immunity acquired.

B. Carrier state: healthy

carriers.

3. Overt (clinical) infection: The outcomes will be: A. Recovery. B. Chronic carrier.

4. Carrier state: Definition of different types of carriers: . incubation carrier . acute carrier . convalescent carrier . chronic carrier

5. Latent infection: After infection, pathogens remain latent inside the body. Develop clinical manifestations when the host immunity has been impaired. Pathogens usually will not be excreted by the host during period of latency.

The Role of Pathogens in the Infection Process:

Invasiveness:⑴ adhesion, penetration ability.

⑵ Virulence: toxins, enzymes, and histolytic ability.

⑶ Infection dose: minimal dose that can

cause an infection. ⑷ Variability: change in structure of the pathogen to evade from host immunity.

The Role of Immune Response in Infection Process:

Differentiation between protective immunity and allergy. . Protective immunity: beneficial . Allergy(anaphylactic reaction): harmful

⑴ Nonspecific immunity: A. Natural barriers: external (skin, mucous membrane, cilia), internal (blood-brain barrier).B. Phagocytosis: macrophages, monocytes, and granulocytes.C. Humoral factors: complements,

interferons, lysozyme, cytokines.

⑵ Specific immunity: Immune respond to specific recognizable antigens. A. Cell-mediated immunity: Important in intracellular infections by viruses, fungi, protozoa and certain bacteria.B. Humoral immunity: Different kinds of antibodies (immune globulins) and their functions.

Pathogenic Mechanisms of Infectious Diseases The occurrence and natural course of infections can be divided into three stages:

1. Portal of entry: Each pathogen has its specific portal of entry. Such as: Mycobacterium tuberculosis, Meningococcus via breath tract. Shigella via digestive tract.

2. Localization and Dissemination

in the host: Specific for each pathogen.

Such as: . Mumps virus in parotid gland. . Hepatitis C virus in the liver. . Shigella in the intestine.

3. Channels of excretion: Important factor for host infectivity. As the source of infection. Such as: . Hepatitis A in the stool. . Hepatitis B in the blood. . Measles virus in expiratory air.

Mechanism of Tissue Damages

1. Direct invasion: Cytolysis, tissue necrosis, inflammation.2.The actions of toxins and cytokines: Resulting in septic shock, Disseminated intravascular coagulation, etc.

Mechanism of Tissue Damages

3. Immunopathogenesis: Immunosuppression, T-cell destruction, immune complexes, antibody-mediated cytotoxicities.

Important Patho-physiologic Changes in infection

1. Fever(pyrexia): Exogenous and endogenous pyrogens.

. Exogenous pyrogens: virus etc.

. Endogenous pyrogens: IL-1, TNF, IL-6, interferon etc.

2. Metabolism changes:

(1) Protein: higher proteins catabolism. “acute” proteins (C-reactive protein, sign of acute inflammation). (2) Carbohydrate: acceleration of glucolysis.

2. Metabolism changes:

(3) Water and electrolytes: dehydration, hypokalemia. (4) Endocrine disturbances: higher anabolism, stress, hyper-corticosteroidemia.

Epidemiological Process of Infectious Diseases and Influencing Factors

Epidemiological Process (course): Definition: case occur, spread. The essential elements of epidemiological process include:

1. Sources of infection: Definition. Human, animal.

Patients:⑴ acute, chronic; typical, atypical(mild, severe).

Subclinical infection:⑵ no symptoms. poliomyelitis.

Carriers:⑶ chronic, typhoid, shigellosis. Infected animals:(natural source)⑷

rabies, plague.

2. Routes of transmission Air, droplets, dusts.⑴

e.g. measles. Water, food, flies(fecal-oral⑵

infection). e.g. typhoid.

Fingers, utensils(contact⑶ infection). e.g. shigellosis, influenza.

⑷ Arthropods. A. Biologic: intermediate hosts. e.g. mosquitoes in malaria, chiggers in scrub typhus. B. Mechanical: passive transfer. e.g. flies in amebiasis.

3. Population susceptibility:

Proportion of susceptibles.

Factors Influencing Epidemiological Process

1. Natural factors: Climatic and geographic factors.. Climatic: season, rain, humidity.. Geographic: endemicity.

2. Social factors: social system, social-economic condition, cultural background.

Characteristics of Infectious Diseases

1. Basic characteristics:(1) Pathogens.(2) Infectivity. (3) Epidemiological features: age, sex, season; imported or endemic; sporadic, epidemic, pandemic, outbreaks.(4) Post-infection immunity.

2. Clinical Characteristics:(1) Development stage: A. Incubation period.B. Prodromal period.C. Symptomatic period. Apparent clinical manifestations.D. Convalescent period.E. Recrudescence or relapse.F. Sequelae.

2. Common symptoms and signs.

⑴ Fever(pyrexia) :

Courses:A. Effervescence: early stage. B. Fastigium: full-blown stage.C. Defervescence: improvement stage

Forms:A. Sustained fever: Difference of body temperature less than 1℃ within 24 hours, over 39℃. e.g. Second week of typhoid.

1 2 3 4 5 6 7

B. Remittent fever: Change of body temperature more than 1 ℃ within 24 hours, the base line higher than normal. e.g. Septicemia.

C. Intermittent fever: Fluctuation between normal temperature and high fever within 24 hours. e.g. Malaria.

D. Relapsing fever: Fever lasting 5~7 days with relapse after several days. e.g. Relapsing fever.

E. Undulent fever: Fever lasting several weeks with relapse after several weeks. e.g. brucellosis.

波状热

F. Irregular fever: Curve of body temperature is irregular. e.g. Brucellosis, septicemia.

G. Saddle-type fever: Fever for several days, then with normal temperature for 1 day, and then relapse. e.g. Dengue.

⑵ Skin rash or eruption: Note appearance type, day of the disease, and distribution.

A. Exanthem: Rash on skin surface. e.g. chickenpox.B. Enanthem: Rash on mucous membrane.

e.g. Koplik spots in measles.

a. Maculopapular rash: e.g. Macula and papule (Maculopapule) in measles; rose spots in typhoid fever.

b. Petechiae: subcutaneous hemorrhages or ecchymosis. e.g. septicemia, typhus, hemorrhagic fever with renal syndrome.

c. Vesiculo-pustule rash: Vesicles and pustules in skin and mucous membrane. e.g. Varicella(chickenpox), herpes zoster, smallpox.

d. Urticaria: Seen in serum sickness, parasitic diseases, drug hypersensitivity, etc.

(3) Toxemic symptoms: A. General presentations: malaise; headache; anorexia; pain in muscles, joints and bones; disturbance in consciousness; meningeal irritation; septic shock; liver and kidney failure, etc.

B. Reticulo-endothelial system reactions: hepatomegaly, splenomegaly, lymphadenopathy.

4. Clinical forms:(1) development: Acute, subacute and chronic forms. (2) forms of clinical manifestation: mild, moderate (typical) or severe forms of the disease. ambulatory form in typhoid (without symptom and signs).

Diagnosis of Infectious Diseases

1. Clinical manifestations(1) Mode of onset(2) Type of fever(3) Accompanying symptoms: headache, myalgia, arthralgia etc.(4) Signs: Consciousness, jaundice, skin rash, buccal membrane, Koplik spot, eschar, subcutaneous hemorrhage, liver, spleen, lymph nodes.

Pathognomonic signs• Measles: Koplik spots• Mumps: swelling of parotid gland• Scrub typhus: eschar• Leptospirosis: myalgia, calf muscle• Typhoid: rose spots• Cysticercosis: subcutaneous nodules• Hepatoencephalopathy: flapping tremor• Schistosomiasis: urticaria• Shigellosis: mucus-pus-bloody stool• Amebic dysentery: strawberry jam-like stool• Rabies: hydrophobia

Characteristic sign of scrub typhus

2. Epidemiological Data:(1) History of contact with similar cases.(2) Occupation, living environment and life style.(3) History of vaccination.(4) History of transfusion of blood or blood products.

3. Laboratory Examinations:(1) Routine examinations: blood, urine, stool. Leukocytosis, leukopenia, eosinopenia, eosinophilia. Biochemical analysis of the blood for liver functions and kidney functions, etc.

Leukocytosis:

• Infection with virus:

epidemic hemorrhagic fever,

Japanese B encephalitis,

infectious mononucleosis.

• Infection with bacteria, etc.

(2) Detection and isolation of pathogens: A. Adequate collection and transportation of specimens.

B. Direct examination: macroscopy: e.g. Ascaris lumbricoides, hook worm, Enterobius vermicularis, etc. microscopy:e.g.Plasmodium,

Cryptococcus neoformans,Mycobacterium tuberculosis

C. Culture by artificial media or tissue culture. Media culture: Entamoeba histolytica, Shigella, Salmonella, etc. Tissue culture: dengue virus, poliovirus, etc.

D. Animal inoculation. Intraperitoneal inoculation: Rickettsia tsutsugamushi. Intracerebral inoculation: encephalitis virus.

E. Specific antigen detection: Methods: agglutination test, ELISA, EIA, FAT, RIA, flow cytometry, etc.

F. Molecular biologic assay: Using isotope or non-isotope probes; Polymerase chain reaction (PCR). Mycobacterium tuberculosis, hepatitis C virus, etc.

PCR techniquePCR technique

PCR体系第一次循环

第二次循环

～30次后 106

dNTPs、Mg2+、Taq酶、模板、引物

(3) Detection of specific antibodies: By means of : ELISA, RIA, etc. IgM, IgG antibodies.

标 记 酶

无色底物

有色底物

抗体抗原

ELISA test

(4) Others: T-cell subset assay: e.g. for AIDS.

Skin test: e.g. for tuberculosis, cysticercosis.

Fibro-optic endoscopy: e.g. for esophageal varices.

Imaging (X-ray, ultrasound,

CT, MR): e.g. for amebic liver abscess.

Biopsy: e.g. for chronic hepatitis.

Treatment of Infectious Diseases

Principles of therapy

1. Aim of treatment: . Not only for alleviation of symptoms and signs, but also for isolation of patients to prevent propagation of infection to the community. . Comprehensive treatmentincludes drug therapy, nursing care and isolation. . Pay attention to both specific and symptomatic treatments.

2. Therapeutic methods:⑴ General and supportive treatment.

Etiologic (specific) treatment.⑵ Symptomatic treatment.⑶ Rehabilitation therapy for⑷

sequelae. Traditional Chinese medicine⑸

and acupuncture.

Prevention of Infectious Diseases

1. Measures against the source of infection:

⑴ Report of cases: According to the Law for Controlling Infectious Diseases issued by the central government.

Three kinds of case report:Kind A: plague, cholera, smallpox. <6hs. Kind B: AIDS, hepatitis, etc. <12hs.Kind C: influenza, mumps, etc. <48hs.

⑵ Isolation of patients: until the patient becomes non-infectious.

(3) Quarantine of contacts: until the incubation period of the infectious disease is over.

⑷ Identification and treatment of carriers.

⑸ Control of infected animals: Eradication or therapy.

2. Interrupt (Block) the routes of transmission:

⑴ General hygienic measures: Clean drinking water supply, food hygiene, correct sewage disposal.

⑵ Disinfection and eradication of insect vectors.

⑶ Intervention of parasite life cycles. e.g. eradication of snails (Oncomelania) in endemic area of schistosomiasis.

3. Protection of the susceptible persons:

⑴ Immunological prophylaxis: . Active (vaccination): intracutaneous inoculation with smallpox vaccine. subcutaneous inoculation with hepatitis B vaccine. . passive (immunoglobulins): intramuscular injection with antibodies against tetanus bacillus.

⑵ Protection from environmental factors: e.g. mosquitoes bites, skin penetration by Leptospira and hookworm larvae.

⑶ Chemo-prophylaxis: artesunate against malaria

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